Abstract
Replicative capacity of a cell is strongly correlated with telomere length regulation. Aberrant lengthening or reduction in the length of telomeres can lead to health anomalies, such as cancer or premature aging. Telomerase is a master regulator for maintaining replicative potential in most eukaryotic cells. It does so by controlling telomere length at chromosome ends. Akin to cancer cells, most single-cell eukaryotic pathogens are highly proliferative and require persistent telomerase activity to maintain constant length of telomere and propagation within their host. Although telomerase is key to unlimited cellular proliferation in both cases, not much was known about the role of telomerase in human parasites (malaria, Trypanosoma, etc.) until recently. Since telomerase regulation is mediated via its own structural components, interactions with catalytic reverse transcriptase and several factors that can recruit and assemble telomerase to telomeres in a cell cycle-dependent manner, we compare and discuss here recent findings in telomerase biology in cancer, aging and parasitic diseases to give a broader perspective of telomerase function in human diseases.
Highlights
The enzymatic repair of the loss of chromosome termini known as ”telomeres” by the RNA-protein enzyme ”telomerase” is an error-prone but highly evolved process that is critical for maintaining genome integrity
While telomerase from different species are highly varied in their structure, process of biogenesis and maturation, there are some universal features of telomerase which are shared between various species
Telomerase and telomere biology have been extensively studied in human and yeast but the same in not true for clinically important eukaryotic pathogens like Plasmodium, Trypanosoma, Toxoplasma, Pneumocystis etc
Summary
The enzymatic repair of the loss of chromosome termini known as ”telomeres” by the RNA-protein enzyme ”telomerase” is an error-prone but highly evolved process that is critical for maintaining genome integrity. The cellular DNA polymerase, which uses short RNA primers to initiate DNA synthesis, was unable to complete the replication at the lagging strand termini of linear DNA [2] This phenomenon is widely known as an “end-replication” problem [2]. Eukaryotic cells needed some special mechanism to protect their chromosomal ends and prevent DNA shortening The solution to this “end-replication problem” came with the discovery of telomerase enzyme in the late 1980 [4,5]. Both in vitro and in vivo, telomerase enzyme activity was found to increase the length of chromosomal termini, the ”telomeres” by addition of repetitive DNA sequences using RNA as a template [4,5,6]. This review will describe the evolution and structure-function relationship of telomerase components and their roles in human diseases with emerging new information on telomerase in parasitic diseases
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.